Giant cell tumor of bone

GIANT CELL TUMOR OF BONE (OSTEOCLASTOMA)

• Giant cell tumor (GCT) is a primary bone neoplasm composed of osteoclast like giant cells and round to oval mononuclear cells involving ends of long bones in skeletally matured patients

• Histogenesis of this tumor is unclear

• Immunohistochemical studies have shown that both mononuclear and giant cells are derived from histiocytes

• These tumors respond peculiarly to dexamethasone therapy indicating that it may not be the neoplasm, but can be example of giant cell reparative granuloma

• Giant cell tumors mostly involve epiphyses but pure metaphyseal giant cell tumor can also occur.

• Incidence – GCT constitutes 5% of primary bone tumors and 20% of benign tumors

• Clinical features

  • Age –common in 3^rd and 4^th decades of life

  • Sex – Slight female predominance probably due to early skeletal maturity in females when compared to male

  • Common presenting symptoms – pain and few of them present with swelling

  • Sites-occurs at the ends of long bones

    • Common site – distal femur followed by proximal tibia,  distal end of radius and sacrum

    • Other less commonly involved sites are

      • Proximal femur (greater trochanter or head)

      • Flat bones like ilium and skull with sphenoid bone as predominant site

      • Small bones of hands and feet- in younger patients with aggressive tumor

    • Multicentre lesions involving small bones may occur

• Radiographic findings:

  • Giant cell tumor in long bones occur as an eccentric, purely cystic lesion involving the end of the bone

  • 50 % of the tumors extend into the articular cartilage and 50% of them have aim of residual subchondral bone

  • 5% of the tumors may involve the joint

  • Cortex is destroyed and the lesion may extend into soft tissues, where the lesion is covered by thin shell of reactive new bone.

  • Periosteal new bone formation is rarely seen

  • GCT do not have rim of sclerosis but when tumor extends into soft tissue, it produces on egg shell of new bone

  • Few GCTs in bone show sclerosis either at periphery or at the centre

  • CT and MRI do not show specific features but are similar to other neoplasms showing dark T1 – weighted images and bright T2 weighted images

  • Radiological staging system for giant cell tumor was proposed by Companaci et al. According to this system

    • Grade -1 well defined lesion with thin sclerotic rim

    • Grade -2 well defined tumor without a sclerotic rim. Cortex is thinned out but intact

    • Grade -3 poorly marginated permeative and aggressive appearing lesion. cortex is destroyed and lesion in soft tissues

  • Grading system has no correlation with prognosis but is helpful in surgical management

• Gross:

  • Usually tumor is received as curettage specimen which  is soft dark brown with areas of yellowish discolouration

  • In resected specimen tumor is situated at the end of long bone

  • Tumor has cystic areas of variable sizes

  • Cortex is thinned out

  • Lesion may extend into the soft tissue

  • Usually lesion is dark brown but some tumors may be fleshy resembling sarcomas

• Microscopic findings:

  • Giant cell tumor are composed of giant cells and mononuclear cells

  • Mononuclear cells –

    • have distinct cell borders, amphophilic to eosinophlic cytoplasm, round to oval nuclei with indistinct nucleoli and uniformly distributed chromatin

    • Mitotic figures are seen (not atypical)

    • Few cells may have enlarged hyperchromatic nuclei

  • Giant cells-

    • More or less uniformly distributed and may contain may nuclei ranging from 40 to 60

    • Nuclear features are similar to those of mononuclear cells

    • Mitotic figures are not seen.

  • Giant cells and mononuclear cells arranged compactly and hence there is no collagen formation

  • Variations which can be seen are

    • Spindle shaped mononuclear cells arranged in storiform pattern similar to fibrohistiocytic tumors. Giant cells are less in this areas.

    • Clusters of foam cells may be present .Mononuclear cells have vacuolated cytoplasm and touton giant cells are noted

    • Secondary aneurysmal bone cyst may occur

    • Reactive bone formation in the form of seems of osteoid rimmed by osteoblasts can be seen and is especially prominent in giant cell tumors of vertebrae

    • Hypocellualr cartilage or microscopic nodules may be seen within the tumor but is uncommon

    • Stroma may show calcification

    • Foci of infarct like necrosis are common

  • Vascular invasion in the soft tissues surrounding giant cell tumor may be found but its correlation with pulmonary metastasis is rare.

• Differential diagnosis:

• Chondroblastoma 

  • Both tumors involve ends of long bones 

  • In GCT epiphyseal plate is closed whereas in chondroblastoma it is open

  • Eosinophilic pink cartilage and “chicken wire”like calcification is seen in chondroblastoma 

  • Nuclei in chondroblastoma are cleaved but in giant cell tumor they are regular and round 

• Aneurysmal bone cyst: 

  • Occurs in skeletally immature patients 

  • Tumor is predominantly metaphyseal 

  • Spindle shaped mononuclear cells produce collagen which is absent in GCT 

  • Loose granulation tissue is seen aneurismal bone cyst but is absent in GCT

• Osteosarcoma with giant cells 

  • Osteosarcoma occur in metaphysic and Pleomorphism in mononuclear cells rules out giant cell tumor 

• Metaphyseal fibrous defect 

  • Occurs in metaphysis and in children 

• Brown tumor of hyperparathyroidism 

  • These tumors have abudance of new bone formation and collagen 

  • Large destructive tumors are rare in hyperparathyroidism 

  • Radiographic features and biochemical abnormalities are helpful in diagnosis

• Treatment & prognosis

  • Surgical treatment is main stay of treatment

  • As tumor occurs close to joint, curettage is preferred to preserve joint

  • Recurrence rate is 25% to 50%

  • Recurrent tumors and large tumors are treated by resection of involved bone segment.

  • Radiotherapy is given t o tumors which cannot be excised

  • Metastasis is seen in less than 3% of tumors

  • Metastasis occurs to lungs and rarely to mediastinal lymphnode

  • Metastasis cannot be predicted by histologic features

  • 25% of patients die with progressive disease, however prognosis in this tumour is unpredictable

Malignancy in giant cell tumor

• Sarcomas arise in GCT

• sarcomas occurring within a giant cell tumor is termed as “primary giant cell tumor” and that arises in the site where previously GCT was diagnosed is termed as “secondary giant cell tumor”

• These patients are decade older than those with GCT

• Sex- slight female predominance

• Recurrence of tumor often long delay should be suspected as malignant change, as GCTS mostly recur with  in 2 years of life

• Site – same as GCTS at the end of long bores. Tumors in distal femur and proximal tibia account for more than half of all cases

• Grossly –primary malignant GCT are similar to GCT where as secondary malignant GCT are fleshy

• Microscopy –

  • primary malignant GCT have areas resembling GCT, juxtaposed with areas showing Pleomorphic spindle cells with or without matrix formation

  • Secondary malignant GCT- do not contain areas simulating GCT but only has sarcomatous areas

  • Clinical history gives clue to diagnosis

• Treatment :

  • Surgical treatment is preferred

  • Prognosis with primary malignant GCT is excellent whereas survival rate in secondary malignant GCT is any 30%

Reference 

• K.Krishnan Unni, Carrie Y. Inwards, Julia A. Bridge, Lars-Gunnar Kindblom, Lester E.Wold. Giant cell tumor. In: Tumors of the Bones and Joints. AFIP Atlas of tumor pathology. Series 4.281-291